The purpose of this program project grant is to investigate the immunobiology and improve the therapeutic effects of syngeneic, autologous, and allogeneic marrow transplantation in clinical malignancy and in disease involving bone marrow failure. The proposal is made up of five projects: (1) Therapeutic Application of Marrow Transplantation and Supportive Program Services; (2) Immunogenetics as Applied to Clinical Bone Marrow Transplantation; (3) Graft-Versus-Host Reaction and Disease (GVHD); (4) Autologous Lympho-hematopoietic Transplantation and (5) Radiotherapy as Applied to Lympho-hematopoietic Transplantation. The objectives of the various projects are: (1) Explore the therapeutic potential of cytoreductive treatment combined with syngeneic, autologous, and allogeneic marrow transplantation in human malignancy and aplastic anemia; (2) identify and characterize non-HLA and HLA-linked factors that are pertinent to engraftment and GVHD; (3) examine in depth the nature, prediction, prevention and treatment of GVHD; (4) further develop the methodology and study the effects of autologous lympho-hematopoietic transplantation in malignancy; and (5) study the effects of fractionated radiotherapy together with chemotherapy in preclinical models.